The death rate due to respiratory disease has increased nearly 20% in the United States since 1979, surpassing virtually all other types of disease. Adult respiratory distress syndrome (ARDS) alone afflicts approximately 150,000 patients every year with a mortality rate between 30 and 70%. Current treatment is limited to extracorporeal membrane oxygenation (ECMO), but ECMO systems are generally assembled from multiple, unmatched components to create a pump-oxygenator circuit. These circuits result in higher than desired priming volume and membrane surface area because of non-optimized blood flow dynamics. In order to overcome these limitations, we have proposed the development of a novel artificial respiratory device capable of sustained respiratory support. The goal of this proposal is to develop an integrated pump-oxygenator (IPO) device, which incorporates durable membranes and magnetically levitated blood pump technology to produce a highly efficient respiratory support system with low priming volumes. Accordingly, our specific aims include the following: Specific Aim 1: Employ fluid simulation methods to model blood pumping function, gas transfer and hemocompatibility, and use these results to design and fabricate oxygenator components with optimal size and operating parameters. Specific Aim 2: Fabricate the components of the IPO prototype device for in-vitro characterization, including an evaluation of device blood flow performance. Specific Aim 3: Evaluate the device in-vitro utilizing bovine blood to assess gas exchange and the effects on blood. Specific Aim 4: Conduct in-vivo animal studies (3) in sheep to assess in-vivo hemodynamics, gas exchange and biocompatibility of the IPO device. Successful completion of this project will result in the development of a portable pump oxygenator system characterized by improved hemocompatibility, due to the use of the MagLev pump, improved oxygen efficiency, due to enhanced blood recirculation and blood flow dynamics, and ease of manufacturing, due to its modular design. We anticipate that such as system will be capable of providing long term respiratory support (weeks to months). The availably of such a device should have significant impact on reducing mortality due to severe, acute respiratory disorders. [unreadable] [unreadable] [unreadable]